The pharmacological management of Lennox-Gastaut syndrome and critical literature review

Alberto Verrotti, Pasquale Striano, Giulia Iapadre, Luca Zagaroli, Paolo Bonanni, Giangennaro Coppola, Maurizio Elia, Oriano Mecarelli, Emilio Franzoni, Paola De Liso, Federico Vigevano, Paolo Curatolo

Research output: Contribution to journalArticle

Abstract

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with a prevalence of 1–2% of all patients with epilepsy. It is characterized by multiple pharmaco-resistant seizure types, including tonic, atypical absences and tonic or atonic drop attacks, and the presence of electroencephalographic abnormalities, such as slow-spike waves and paroxysmal fast rhythms. Intellectual disability, behavioural and psychiatric disorders are common comorbidities; these disturbances have a multi-factorial pathogenesis. The selection of the most appropriate drug must be tailored to each patient and guided by the prevalent seizure type. In this paper available pharmacological options are discussed and for each pharmacological agent, current evidence of efficacy and tolerability is provided. Valproic acid represents one of the first-line options in the treatment of LGS. Anyway, other antiepileptic drugs (AEDs) may be considered and added: lamotrigine, rufinamide, topiramate, clobazam can be efficacious. The use of felbamate must be carefully evaluated because of its adverse events. Perampanel, zonisamide, levetiracetam and fenfluramine have shown to be useful in the treatment of selected patients; nevertheless, the lack of RCTs does not allow to recommend their use in a systematic way. Recently, cannabidiol has provided high evidence of efficacy against LGS seizures; however, these data must be confirmed by long-term extensive studies and by trials comparing different AEDs, one to each other.
Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalSeizure : the journal of the British Epilepsy Association
Volume63
DOIs
Publication statusPublished - Dec 1 2018

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Seizures
zonisamide
etiracetam
felbamate
Pharmacology
Anticonvulsants
Cannabidiol
Fenfluramine
Syncope
Valproic Acid
Brain Diseases
Intellectual Disability
Psychiatry
Comorbidity
Epilepsy
Therapeutics
Pharmaceutical Preparations
Lennox Gastaut Syndrome
rufinamide
clobazam

Keywords

  • Antiepileptic therapy, Cannabidiol, Drop attack, Epileptic encephalopathy, Fenfluramine, Lennox-Gastaut syndrome

Cite this

The pharmacological management of Lennox-Gastaut syndrome and critical literature review. / Verrotti, Alberto; Striano, Pasquale; Iapadre, Giulia; Zagaroli, Luca; Bonanni, Paolo; Coppola, Giangennaro; Elia, Maurizio; Mecarelli, Oriano; Franzoni, Emilio; Liso, Paola De; Vigevano, Federico; Curatolo, Paolo.

In: Seizure : the journal of the British Epilepsy Association, Vol. 63, 01.12.2018, p. 17-25.

Research output: Contribution to journalArticle

Verrotti, Alberto ; Striano, Pasquale ; Iapadre, Giulia ; Zagaroli, Luca ; Bonanni, Paolo ; Coppola, Giangennaro ; Elia, Maurizio ; Mecarelli, Oriano ; Franzoni, Emilio ; Liso, Paola De ; Vigevano, Federico ; Curatolo, Paolo. / The pharmacological management of Lennox-Gastaut syndrome and critical literature review. In: Seizure : the journal of the British Epilepsy Association. 2018 ; Vol. 63. pp. 17-25.
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AB - Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with a prevalence of 1–2% of all patients with epilepsy. It is characterized by multiple pharmaco-resistant seizure types, including tonic, atypical absences and tonic or atonic drop attacks, and the presence of electroencephalographic abnormalities, such as slow-spike waves and paroxysmal fast rhythms. Intellectual disability, behavioural and psychiatric disorders are common comorbidities; these disturbances have a multi-factorial pathogenesis. The selection of the most appropriate drug must be tailored to each patient and guided by the prevalent seizure type. In this paper available pharmacological options are discussed and for each pharmacological agent, current evidence of efficacy and tolerability is provided. Valproic acid represents one of the first-line options in the treatment of LGS. Anyway, other antiepileptic drugs (AEDs) may be considered and added: lamotrigine, rufinamide, topiramate, clobazam can be efficacious. The use of felbamate must be carefully evaluated because of its adverse events. Perampanel, zonisamide, levetiracetam and fenfluramine have shown to be useful in the treatment of selected patients; nevertheless, the lack of RCTs does not allow to recommend their use in a systematic way. Recently, cannabidiol has provided high evidence of efficacy against LGS seizures; however, these data must be confirmed by long-term extensive studies and by trials comparing different AEDs, one to each other.

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